Method for inhibiting activation of the human A3 adenosine receptor to treat asthma

Abstract

The invention is a method for inhibiting activation of the human A3 adenosine receptor with adenosine, by treating the receptor a compound of the formula <IMAGE> <IMAGE> to treat asthma.

What is claimed is: 
     
       1. A method for treating or preventing asthma in a patient comprising administering to the patient a compound of the formula ##STR13## and pharmaceutically acceptable salts, wherein R 1  is (a) phenyl or pyrimidyl optionally substituted with one or two substituents selected from the group consisting essentially of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl, or   (b) furyl, thiophenyl or thiazolyl optionally susbtituted with C 1  -C 4  -alkyl or phenyl;   R 2  is hydrogen, C 1  -C 4  -alkyl or phenyl;     R 3  is --CN, --COOC 1-4  alkyl, --CONH 2 , --COOH, --CONHSO 2  R 5  or 5-tetrazolyl;     R 4  is --C 1-4  -alkyl optionally substituted with --COOC 1-4  alkyl, --CONH 2 , COOH or phenyl optionally substituted with one or two substituents selected from the group consisting essentially of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl; and     R 5  is --C 1  -C 4  -alkyl or phenyl optionally substituted with one or two substituents selected from the group consisting essentially of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl.     
     
     
       2. A method of claim 1, wherein the compound has the formula ##STR14## and pharmaceutically acceptable salts, wherein R 1  is phenyl optionally substituted wiffi one or two substituents selected from the group consisting of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl, or   R 2  is hydrogen, C 1  -C 4  -alkyl or phenyl;     R 3  is --CN, --COOC 1-4  alkyl, --CONH 2 , --COOH , --CONHSO 2  R 5  or 5-tetrazolyl;     R 4  is C 1-4  -alkyl optionally substituted with --COOC 1-4  alkyl, --CONH 2 , COOH or phenyl, optionally substituted with one or two substituents selected from the group consisting of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl; and     R 5  is C 1  -C 4  -alkyl or phenyl optionally substituted with one or two substituents selected from the group consisting of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl.     
     
     
       3. A method of claim 2, wherein the compound has the formula ##STR15## and pharmaceutically acceptable salts, wherein R 1  is phenyl optionally substituted with one or two substituents selected from the group consisting of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl, or   R 2  is hydrogen, C 1  -C 4  -alkyl or phenyl;     R 3  is --COOCH 3  or --COOCH 2  CH 3  ;     R 4  is --CH 3 , --CH 2  CH 3 , --CH 2  COOCH 3 , --CH 2  COOC(CH 3 ) 3 , --CH 2  COOH, -benzyl, 4-bromobenzyl or 4-chlorobenzyl; and     R 5  is C 1  -C 4  -alkyl or phenyl optionally substituted with one or two substituents selected from the group consisting of C 1  -C 4  -alkyl, bromo, chloro, fluoro, CF 3 , C 1  -C 4  -alkoxy and phenyl.     
     
     
       4. A method of claim 3, wherein the compound has the formula ##STR16## and pharmaceutically acceptable salts. 
     
     
       5. A method of claim 4, wherein the salt is the pharmaceutically acceptable salt is the methanesulfonic acid salt.